Several points in the cell cycle are potential targets for developmental regulation, but the transition from the first gap phase of the cell cycle, G1, to S phase, or DNA synthesis, may be critical for coordinating regulatory inputs, and, eventually, cell proliferation. Despite the crucial nature of this transition, the molecules involved in its regulation and the mechanisms underlying it and linking DNA synthesis to growth control are just beginning to be understood. Genetical approaches in yeast and biochemistry in mammalian tissue culture systems have yielded invaluable information, but a classical genetic screen for regulators of G1/S transitions in a metazoan has not yet been performed. Thus, I propose to carry out such a screen, and to subsequently characterize the molecules of interest as a first step toward understanding the developmental regulation of the cell cycle. The first part is a screen of ethylmethane sulphonate-induced mutants of Drosophila melanogaster for those potentially defective in G1/S transitions. Based on several criteria we predict that one phenotype of these mutants will be a first-instar larval growth arrest. Because this arrest need not be a result specifically of defects at G1/S transitions, the second aim of this proposal is to develop, refine, and execute assays to identify mutants which are specifically defective in traversing the G1/S boundary. The final aims of the project are to order the mutants in a pathway leading to DNA synthesis, and to use this information to begin to clone these genes.